Solution NMR to Quantify Mobility in Membranes: Diffusion, Protrusion, and Drug Transport Processes

Lipid bilayer membranes are soft, fluid, and dynamic architecture where molecules are constantly moving and thermally fluctuating under physiological conditions. In this review, a strategy to quantify molecular dynamics in membranes is introduced by utilizing solution-state NMR spectroscopy as a versatile, noninvasive technique. The dynamics involves lateral diffusion and protrusion motion, in parallel and vertical direction to the membrane surface. Dynamical behavior of small-sized drugs, chemicals, and peptides is also reviewed in relation to the lipid movements in membranes, on the basis of recent multinuclear NMR in combination with the pulsed field gradient technique. Finally, in-cell NMR method is introduced as a promising technique to capture drug transport processes in real time, to shed light on mechanisms of deliveries to living cells without perturbation of the system.